Maintaining cardiac homeostasis by translational selenium nanoparticles with rapid selenoproteins regulation to achieve radiation-induced heart prevention

Abstract

Radiation-induced heart disease (RIHD) typically manifests as severe oxidative stress and immune dysregulation, which are serious sequela affecting cancer patients. Therefore, developing radioprotector that capable of inhibiting oxidative stress and regulating the immune microenvironment simultaneously is urgently desired. Selenium (Se), as the active center of antioxidant selenoproteins, is widely recognized as a promising therapeutic element in antioxidative stress therapy. Therefore, translational elemental Se nanoparticles decorated by lentinan (Se@LET) was developed and its preventive efficacy and mechanism in RIHD were systematically analyzed by comparing with four types of organic Se. In vitro experiments revealed because its rapid biotransformation to antioxidant selenoproteins, Se@LET alleviated the overproduction of ROS caused by X-Ray and further prevented G2/M phase arrest and DNA damage in cells, thus achieving superior heart prevention than other organic selenides. Meanwhile, Se@LET effectively regulated macrophage polarization and inhibit radiation-induced inflammation. Consequently, the administration of Se@LET before and after radiation showed outstanding protective effects on RIHD in vivo by regulating myocardial immunosuppressive microenvironment, but also suppressed the side effects of X-Ray. Collectively, this study demonstrates a valuable strategy for irradiation prevention by using translational element Se nanospecies and provides an attractive clinical alternative for heart protection to prevent RIHD.